tbuckley/cabot-search huggingface dataset:
Bionic peptide scaffold in situ polarization and recruitment of M2 macrophages to promote peripheral nerve regeneration
Authors: Pengxiang Yang, Yong Peng, Xiu Dai, Jing Jie, Deling Kong, Xiaosong Gu, Yumin Yang
Journal: Bioactive Materials (2023)

Tissue regeneration requires exogenous and endogenous signals, and there is increasing evidence that the exogenous microenvironment may play an even more dominant role in the complex process of coordinated multiple cells. The short-distance peripheral nerve showed a spontaneous regenerative phenomenon, which was initiated by the guiding role of macrophages. However, it cannot sufficiently restore long-distance nerve injury by itself. Based on this principle, we firstly constructed a proinflammatory model to prove that abnormal M2 expression reduce the guidance and repair effect of long-distance nerves. Furthermore, a bionic peptide hydrogel scaffold based on self-assembly was developed to envelop M2-derived regenerative cytokines and extracellular vesicles (EVs). The cytokines and EVs were quantified to mimic the guidance and regenerative microenvironment in a direct and mild manner. The bionic scaffold promoted M2 transformation in situ and led to proliferation and migration of Schwann cells, neuron growth and motor function recovery. Meanwhile, the peptide scaffold combined with CX3CL1 recruited more blood-derived M2 macrophages to promote long-distance nerve reconstruction. Overall, we systematically confirmed the important role of M2 in regulating and restoring the injury peripheral nerve. This bionic peptide hydrogel scaffold mimicked and remodeled the local environment for M2 transformation and recruitment, favoring long-distance peripheral nerve regeneration. It can help to explicate regulative effect of M2 may be a cause not just a consequence in nerve repair and tissue integration, which facilitating the development of pro-regenerative biomaterials.
Chromosome-Aware Phylogenomics of Assassin Bugs (Hemiptera: Reduvioidea) Elucidates Ancient Gene Conflict
Authors: Alexander Knyshov, Eric R L Gordon, Paul K Masonick, Stephanie Castillo, Dimitri Forero, Rochelle Hoey-Chamberlain, Wei Song Hwang, Kevin P Johnson, Alan R Lemmon, Emily Moriarty Lemmon, Samantha Standring, Junxia Zhang, Christiane Weirauch
Journal: Molecular Biology and Evolution (2023)

Though the phylogenetic signal of loci on sex chromosomes can differ from those on autosomes, chromosomal-level genome assemblies for nonvertebrates are still relatively scarce and conservation of chromosomal gene content across deep phylogenetic scales has therefore remained largely unexplored. We here assemble a uniquely large and diverse set of samples (17 anchored hybrid enrichment, 24 RNA-seq, and 70 whole-genome sequencing samples of variable depth) for the medically important assassin bugs (Reduvioidea). We assess the performance of genes based on multiple features (e.g., nucleotide vs. amino acid, nuclear vs. mitochondrial, and autosomal vs. X chromosomal) and employ different methods (concatenation and coalescence analyses) to reconstruct the unresolved phylogeny of this diverse (∼7,000 spp.) and old (>180 Ma) group. Our results show that genes on the X chromosome are more likely to have discordant phylogenies than those on autosomes. We find that the X chromosome conflict is driven by high gene substitution rates that impact the accuracy of phylogenetic inference. However, gene tree clustering showed strong conflict even after discounting variable third codon positions. Alternative topologies were not particularly enriched for sex chromosome loci, but spread across the genome. We conclude that binning genes to autosomal or sex chromosomes may result in a more accurate picture of the complex evolutionary history of a clade.
Prognostic Markers of DNA Methylation and Next-Generation Sequencing in Progressive Glioblastoma from the EORTC-26101 Trial
Authors: Tobias Kessler, Daniel Schrimpf, Laura Doerner, Ling Hai, Leon D. Kaulen, Jakob Ito, Martin van den Bent, Martin Taphoorn, Alba A. Brandes, Ahmed Idbaih, Julien Dômont, Paul M. Clement, Mario Campone, Martin Bendszus, Andreas von Deimling, Felix Sahm, Michael Platten, Wolfgang Wick, Antje Wick
Journal: Clinical Cancer Research (2023)

Abstract Purpose: The EORTC-26101 study was a randomized phase II and III clinical trial of bevacizumab in combination with lomustine versus lomustine alone in progressive glioblastoma. Other than for progression-free survival (PFS), there was no benefit from addition of bevacizumab for overall survival (OS). However, molecular data allow for the rare opportunity to assess prognostic biomarkers from primary surgery for their impact in progressive glioblastoma. Experimental Design: We analyzed DNA methylation array data and panel sequencing from 170 genes of 380 tumor samples of the EORTC-26101 study. These patients were comparable with the overall study cohort in regard to baseline characteristics, study treatment, and survival. Results: Of patients' samples, 295/380 (78%) were classified into one of the main glioblastoma groups, receptor tyrosine kinase (RTK)1, RTK2 and mesenchymal. There were 10 patients (2.6%) with isocitrate dehydrogenase mutant tumors in the biomarker cohort. Patients with RTK1 and RTK2 classified tumors had lower median OS compared with mesenchymal (7.6 vs. 9.2 vs. 10.5 months). O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation was prognostic for PFS and OS. Neurofibromin (NF)1 mutations were predictive of response to bevacizumab treatment. Conclusions: Thorough molecular classification is important for brain tumor clinical trial inclusion and evaluation. MGMT promoter methylation and RTK1 classifier assignment were prognostic in progressive glioblastoma. NF1 mutation may be a predictive biomarker for bevacizumab treatment.
2023 AHA/ACC Clinical Performance and Quality Measures for Coronary Artery Revascularization
Authors: Gregory J. Dehmer, Cindy L. Grines, Faisal G. Bakaeen, Dorian L. Beasley, Theresa M. Beckie, Jack Boyd, Joaquin E. Cigarroa, Sandeep R. Das, Rebecca L. Diekemper, Jennifer Frampton, Connie N. Hess, Nkechinyere Ijioma, Jennifer S. Lawton, Binita Shah, Nadia R. Sutton
Journal: Journal of the American College of Cardiology (2023)
Helix tack-and-suture device for mucosal defect closure following colorectal endoscopic submucosal dissection: is it ready for global adoption?
Authors: Saif Ullah, Faisal S. Ali, Maral Ostovan, Bing-Rong Liu
Journal: Endoscopy (2023)

See also: A novel through-the-scope helix tack-and-suture device for mucosal defect closure following colorectal endoscopic submucosal dissection: a multicenter studyEndoscopy 2023; 55(06): 571-577DOI: 10.1055/a-1970-5528 See also: Reply to Liu et al.Endoscopy 2023; 55(08): 781-781DOI: 10.1055/a-2055-9966
What we should expect from artificial intelligence in video capsule endoscopy
Authors: Cristiano Spada, Silvia Pecere, Stefania Piccirelli, Guido Costamagna
Journal: Endoscopy (2023)

See also: Artificial intelligence-based diagnosis of abnormalities in small-bowel capsule endoscopyEndoscopy 2023; 55(01): 44-51DOI: 10.1055/a-1881-4209
Population health outcomes in South Korea 1990–2019, and projections up to 2040: a systematic analysis for the Global Burden of Disease Study 2019
Authors: Seoyeon Park, Min Seo Kim, Dong Keon Yon, Seung Won Lee, Joseph L Ward, Susan A McLaughlin, Max L Mehlman, Ai Koyanagi, Lee Smith, Louis Jacob, Suneth Buddhika Agampodi, Maryam Beiranvand, Dong-Woo Choi, Sung Hwi Hong, Mehdi Hosseinzadeh, Cho-il Kim, Gyu Ri Kim, Jihee Kim, Kwanghyun Kim, Sungroul Kim, Doo Woong Lee, Hankil Lee, Sang-woong Lee, Yo Han Lee, Ali H Mokdad, Christopher J L Murray, Akinkunmi Paul Okekunle, Eun-Cheol Park, Navid Rabiee, Youn Ho Shin, Simon I Hay, Jae Il Shin
Journal: The Lancet Public Health (2023)

South Korea has one of the longest operating universal health coverage (UHC) systems. A comprehensive analysis of long-term trajectories of morbidity and mortality in the South Korean population after the inception of UHC is needed to inform health-care policy and practice.We used data from the Global Burden of Disease Study (GBD) 2019 to present estimates of cause-specific mortality, incidence, prevalence, years of life lost (YLLs), years of life lived with disability, and disability-adjusted life-years (DALYs) in South Korea from 1990 to 2019. We also examined forecasted estimates of YLLs up to 2040 to investigate likely future changes in disease burden. Finally, we evaluated GBD estimates from seven comparator countries to place disease burden in South Korea within a broader context.Age-standardised DALYs related to non-communicable diseases (NCDs) decreased by 43·6% (95% uncertainty interval [UI] 39·4-47·9) and mortality by 58·8% (55·9-60·5) from 1990 to 2019. In 2019, the ratio of male to female age-standardised rates of YLLs in South Korea was higher than the global average for 75·9% (22 of 29 diseases) of leading causes, indicating a disproportional disease burden on males in South Korea. Among risk factors, tobacco use accounted for the highest number of 2019 deaths (44 470 [95% UI 37 432-53 989]) in males and high systolic blood pressure for the highest number (21 014 [15 553-26 723]) in females. Among the top ten leading causes of YLLs forecast in South Korea in 2040, nine were NCDs, for both males and females.Our report shows a positive landscape of population health outcomes in South Korea following the establishment of UHC. However, due in part to the effects of population ageing driving up medical expenditures for NCDs, financial pressures and sustainability challenges associated with UHC are pressing concerns. Policy makers should work to tackle population ageing and allocate resources efficiently by prioritising interventions that address the leading causes of death and disability identified in this study.Bill & Melinda Gates Foundation.
Mortality in the US Populations With Monoclonal Gammopathy of Undetermined Significance
Authors: Mengmeng Ji, John H. Huber, Martin W. Schoen, Kristen M. Sanfilippo, Graham A. Colditz, Shi-Yi Wang, Su-Hsin Chang
Journal: JAMA Oncology (2023)

This cohort study analyzes a nationally representative sample with a screening test for monoclonal gammopathy of undetermined significance (MGUS) to evaluate overall survival of populations with MGUS compared with those without MGUS among the general population in the US.
Vigorous Intermittent Lifestyle Physical Activity and Cancer Incidence Among Nonexercising Adults
Authors: Emmanuel Stamatakis, Matthew N. Ahmadi, Christine M. Friedenreich, Joanna M. Blodgett, Annemarie Koster, Andreas Holtermann, Andrew Atkin, Vegar Rangul, Lauren B. Sherar, Armando Teixeira-Pinto, Ulf Ekelund, I-Min Lee, Mark Hamer
Journal: JAMA Oncology (2023)

Vigorous physical activity (VPA) is a time-efficient way to achieve recommended physical activity (PA) for cancer prevention, although structured longer bouts of VPA (via traditional exercise) are unappealing or inaccessible to many individuals.To evaluate the dose-response association of device-measured daily vigorous intermittent lifestyle physical activity (VILPA) with incident cancer, and to estimate the minimal dose required for a risk reduction of 50% of the maximum reduction.This was a prospective cohort analysis of 22 398 self-reported nonexercising adults from the UK Biobank accelerometry subsample. Participants were followed up through October 30, 2021 (mortality and hospitalizations), or June 30, 2021 (cancer registrations).Daily VILPA of up to 1 and up to 2 minutes, assessed by accelerometers worn on participants' dominant wrist.Incidence of total cancer and PA-related cancer (a composite outcome of 13 cancer sites associated with low PA levels). Hazard ratios and 95% CIs were estimated using cubic splines adjusted for age, sex, education level, smoking status, alcohol consumption, sleep duration, fruit and vegetable consumption, parental cancer history, light- and moderate-intensity PA, and VPA from bouts of more than 1 or 2 minute(s), as appropriate.The study sample comprised 22 398 participants (mean [SD] age, 62.0 [7.6] years; 10 122 [45.2%] men and 12 276 [54.8%] women; 21 509 [96.0%] White individuals). During a mean (SD) follow-up of 6.7 (1.2) years (149 650 person-years), 2356 total incident cancer events occurred, 1084 owing to PA-related cancer. Almost all (92.3%) of VILPA was accrued in bouts of up to 1 minute. Daily VILPA duration was associated with outcomes in a near-linear manner, with steeper dose-response curves for PA-related cancer than total cancer incidence. Compared with no VILPA, the median daily VILPA duration of bouts up to 1 minute (4.5 minutes per day) was associated with an HR of 0.80 (95% CI, 0.69-0.92) for total cancer and 0.69 (95% CI, 0.55-0.86) for PA-related cancer. The minimal dose was 3.4 minutes per day for total (HR, 0.83; 95% CI, 0.73-0.93) and 3.7 minutes for PA-related (HR, 0.72; 95% CI, 0.59-0.88) cancer incidence. Findings were similar for VILPA bout of up to 2 minutes.The findings of this prospective cohort study indicate that small amounts of VILPA were associated with lower incident cancer risk. Daily VILPA may be a promising intervention for cancer prevention in populations not able or motivated to exercise in leisure time.
Immunoglobulin <scp>G4</scp> in eosinophilic esophagitis: Immune complex formation and correlation with disease activity
Authors: Jonathan G. Medernach, Rung‐Chi Li, Xiao‐Yu Zhao, Bocheng Yin, Emily A. Noonan, Elaine F. Etter, Shyam S. Raghavan, Larry C. Borish, Jeffrey M. Wilson, Barrett H. Barnes, Thomas A. E. Platts‐Mills, Sarah E. Ewald, Bryan G. Sauer, Emily C. McGowan
Journal: Allergy (2023)

Abstract Background Recent studies have shown deposition of immunoglobulin G4 (IgG4) and food proteins in the esophageal mucosa of eosinophilic esophagitis (EoE) patients. Our aims were to assess whether co‐localization of IgG4 and major cow's milk proteins (CMPs) was associated with EoE disease activity and to investigate the proteins enriched in proximity to IgG4 deposits. Methods This study included adult subjects with EoE ( n = 13) and non‐EoE controls ( n = 5). Esophageal biopsies were immunofluorescence stained for IgG4 and CMPs. Co‐localization in paired samples from active disease and remission was assessed and compared to controls. The proteome surrounding IgG4 deposits was evaluated by the novel technique, AutoSTOMP. IgG4‐food protein interactions were confirmed with co‐immunoprecipitation and mass spectrometry. Results IgG4‐CMP co‐localization was higher in the active EoE group compared to paired remission samples (Bos d 4, p = .02; Bos d 5, p = .002; Bos d 8, p = .002). Co‐localization was also significantly higher in the active EoE group compared to non‐EoE controls (Bos d 4, p = .0013; Bos d 5, p = .0007; Bos d 8, p = .0013). AutoSTOMP identified eosinophil‐derived proteins (PRG 2 and 3, EPX, RNASE3) and calpain‐14 in IgG4‐enriched areas. Co‐immunoprecipitation and mass spectrometry confirmed IgG4 binding to multiple food allergens. Conclusion These findings further contribute to the understanding of the interaction of IgG4 with food antigens as it relates to EoE disease activity. These data strongly suggest the immune complex formation of IgG4 and major cow's milk proteins. These immune complexes may have a potential role in the pathophysiology of EoE by contributing to eosinophil activation and disease progression.
A Pilot Study Omitting Radiation in the Treatment of Children with Newly Diagnosed Wnt-Activated Medulloblastoma
Authors: Kenneth J. Cohen, Vasu Munjapara, Dolly Aguilera, Robert C. Castellino, Stacie L. Stapleton, Daniel Landi, David M. Ashley, Fausto J. Rodriguez, Cynthia Hawkins, Edward Yang, Wendy London, Susan Chi, Pratiti Bandopadhayay
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Treatment of wingless (WNT)-activated medulloblastoma (WNT+MB) with surgery, irradiation (XRT), and chemotherapy results in excellent outcomes. We studied the efficacy of therapy de-intensification by omitting XRT entirely in children with WNT+MB. Patients and Methods: Tumors were molecularly screened to confirm the diagnosis of WNT+MB. Eligible children were treated within 31 days following surgery with nine cycles of adjuvant chemotherapy per ACNS0331. No XRT was planned. The primary endpoint was the occurrence of relapse, progression, or death in the absence of XRT within the first two years after study enrollment. Four events in the first 10 evaluable patients would result in early study closure. Results: Fourteen children were prescreened, and nine met the protocol definition of WNT+MB. Six of the nine eligible patients consented to protocol therapy, and five completed planned protocol therapy. The first two children enrolled relapsed shortly after therapy completion with local and leptomeningeal recurrences. The study was closed early due to safety concerns. Both children are surviving after XRT and additional chemotherapy. A third child relapsed at completion of therapy but died of progressive disease 35 months from diagnosis. Two children finished treatment but immediately received post-treatment XRT to guard against early relapse. The final child's treatment was aborted in favor of a high-dose therapy/stem cell rescue approach. Although OS at 5 years is 83%, no child received only planned protocol therapy, with all receiving eventual XRT and/or alternative therapy. Conclusions: Radiotherapy is required to effectively treat children with WNT-altered medulloblastoma. See related commentary by Gottardo and Gajjar, p. 4996
CMR Is Often Abnormal Despite Normal Echocardiography in Suspected Myocardial Infarction With Nonobstructed Coronary Arteries
Authors: Martin G. Sundqvist, Peder Sörensson, Christina Ekenbäck, Magnus Lundin, Stefan Agewall, Elin Bacsovics Brolin, Kerstin Cederlund, Olov Collste, Maria Daniel, Jens Jensen, Shams Y-Hassan, Loghman Henareh, Claes Hofman-Bang, Patrik Lyngå, Eva Maret, Nondita Sarkar, Jonas Spaak, Oscar Winnberg, Kenneth Caidahl, Martin Ugander, Per Tornvall
Journal: JACC. Cardiovascular imaging (2023)
Orexin Agonists — Two Steps Forward, One Step Back
Authors: Nathaniel S. Marshall, Ronald R. Grunstein
Journal: New England Journal of Medicine (2023)

In 1880, Gélineau described a rare syndrome characterized by severe sleepiness with attacks of sleep at inappropriate times during the day and cataplexy, a sudden loss of muscle tone related to emotion; he called this syndrome narcolepsy.1 Patients with narcolepsy also have visual dreamlike hallucinations and sleep paralysis (both characteristic of rapid-eye-movement [REM] sleep), the presence of the HLA-DQB1*06:02 variant, and disturbed nocturnal sleep. This "classic" form of narcolepsy is now called narcolepsy type 1. Narcolepsy type 2 is characterized by sleepiness, aberrant REM periods at the onset of sleep, and no cataplexy. In another syndrome, idiopathic hypersomnia, patients are . . .
Assessment of laparoscopic intracorporeal intestinal anastomosis training using simulation-based 3D printed models: exploring surgical performance and learning curves
Authors: Jianfu Xia, Junjie Wu, Hao Chen, Jinlei Mao, Xiaodong Xu, Jing Zhang, Jin Yang, Zhifei Wang
Journal: International Journal of Surgery (2023)

Intestinal anastomosis is a clinical procedure widely used to reconstruct the digestive tract, but authentic laparoscopic intracorporeal intestinal anastomosis (LIIA) models are lacking. However, three-dimensional (3D) printing can enable authentic and reusable models. In this paper, a novel cost-effective 3D-printing training model of LIIA is designed and the authenticity and validity of the model are tested.A fused deposition modeling 3D printing and an assembled lab model were built to test LIIA. Fifteen surgeons were required to perform LIIA, and their operation score and time were recorded and analyzed. Five experts were invited to assess the face and content validity of the models. A study was also performed to further evaluate and validate the learning curve of surgeons.The difference in modified anastomosis objective structured assessment of technical skills (MAOSATS) scores between the expert, intermediate, and novice groups were significant (64.1±1.8: 48.5±1.7: 29.5±3.1, P <0.001). In addition, the operation time of the procedure was statistically different for all three groups (21.5±1.9: 30.6±2.8:70.7±4.0, P<0.001 ). The five experts rated the face and content validity of the model very highly, with the median being four out of five. Surgeons who underwent repeated training programs showed improved surgical performance. After eight training sessions, the novices' performance was similar to that of the average level of untrained intermediates, while the operation scores of the intermediates were close to that of the average level of experts.In this study, it is found that the LIIA model exhibits excellent face, content, and construct validity. Repeated simulation training of the LIIA training program improved the surgeon's operative performance, so the model is considered one of the most effective methods for LIIA training and assessment of surgical quality in the future and for reducing healthcare costs.
Classification of Breast Cancer According to ERBB2 Immunohistochemistry Scores—Reply
Authors: Frederick M. Howard, Daniel S. Peiffer, Dezheng Huo
Journal: JAMA Oncology (2023)

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